Asthma is considered a chronic inflammatory disease. It involves complex interactions between exogenous [environmental] and endogenous [genetic] factors. The long-term objective of this research is to understand the molecular mechanisms by which environmental exposures can influence the development of asthma. CD 14 is the main receptor for LPS and other bacterial "danger" signals. Our group has found five polymorphisms in the promoter region of the CD14 gene (positions -159, -809, -1145, -1359, -1619 from the transcription start site). We hypothesize that polymorphisms in the promoter region of the CD 14 gene may alter expression of CD 14, and this in turn could alter an individuals sensitivity to LPS exposure. This proposal is for career development in the area of Molecular Epidemiology, which is designed to integrate Epidemiology and Molecular Biology through research and didactic training. The research aims of this project are (1) to determine the association between an acute response to LPS inhalation and genetic polymorphisms in the CD 14 gene; (2) to elucidate the specific role of the CD 14 polymorphisms in CD 14 gene transcription in the context of a population; and (3) to associate an individual's CD 14 transcriptional activity with serum CD 14 and membrane CD 14 accumulation as a function of CD 14 promoter genotypes and putative haplotypes. The didactic goals of this grant are (1) to complete a Masters degree in Epidemiology; (2) to develop and teach a 16-week course on Molecular Epidemiology; (3) to join the International Molecular Epidemiology Task Force; and (4) to attend conferences/short courses on Molecular Epidemiology, Genetic Epidemiology, Occupational Exposures and/or Respiratory Disease. Completion of these research and, didactic goals will allow the candidate to become an independent researcher in the field of Molecular Epidemiology, with particular emphasis on the study of the molecular biology of genes that influence respiratory diseases.